We are studying the ets family of transcription factors and their possible role in human malignancies. The focus of our work in the past few years has been the ERF gene, a new ets-domain protein that we identified in this Laboratory. ERF is a potent transcriptional repressor that can act as a tumor-suppressor gene in certain in vitro systems (ras-transformed NIH3T3 cells). The activity of ERF is regulated by the Erk kinases which can associate and phosphorylate the protein in vivo and in vitro. Data from our lab and that of our collaborators (G. Rubin, UCSF; M. McMahon, DNAX) indicate that ERF is an effector protein in the RAS/RAF signaling pathway. Our current efforts are aiming to determine the function of ERF, the mechanism of its regulation, and its possible association with human malignancies. To that extent we analyzed its physical association with other proteins by the yeast two-hybrid system and GST-fusion protein "pull down", and its subcellular trafficking by immuno- fluorescence in the context of its phosphorylation. We are also in the process of generating a KO mouse and looking into human pathologies associated with chr19q13.1-13.2 where the ERF gene is localized.